AU766533B2 - New tri-substituted phenyl derivatives and analogues - Google Patents

New tri-substituted phenyl derivatives and analogues Download PDF

Info

Publication number: AU766533B2
Authority: AU; Australia
Prior art keywords: oxy; phenyl; methylsulfonyl; ethyl; ethoxy
Prior art date: 1999-12-03
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Ceased

Application number

AU20351/01A

Other languages

English (en)

Other versions

AU2035101A (en

Inventor

Maria Boije

Jonas Fagerhag

Eva-Lotte Lindstedt Alstermark

Bengt Ohlsson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

AstraZeneca AB

Original Assignee

AstraZeneca AB

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-12-03

Filing date

2000-11-29

Publication date

2003-10-16

2000-11-29 Application filed by AstraZeneca AB filed Critical AstraZeneca AB

2001-06-12 Publication of AU2035101A publication Critical patent/AU2035101A/en

2003-10-16 Application granted granted Critical

2003-10-16 Publication of AU766533B2 publication Critical patent/AU766533B2/en

2020-11-29 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

-1 tri-substituted phenyl Chemical class 0.000 title description 26
150000001875 compounds Chemical class 0.000 claims description 105
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 18
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 14
150000003839 salts Chemical group 0.000 claims description 13
230000002829 reductive effect Effects 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
239000000651 prodrug Chemical group 0.000 claims description 11
229940002612 prodrug Drugs 0.000 claims description 11
102000004877 Insulin Human genes 0.000 claims description 9
108090001061 Insulin Proteins 0.000 claims description 9
229940125396 insulin Drugs 0.000 claims description 9
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
238000011321 prophylaxis Methods 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 4
230000035945 sensitivity Effects 0.000 claims description 4
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
230000003287 optical effect Effects 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
239000012453 solvate Chemical group 0.000 claims description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
239000002671 adjuvant Substances 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
VLJZDMUHOYNAJU-UHFFFAOYSA-N ethyl 3-[4-benzyl-3-[2-(4-methylsulfonyloxyphenyl)ethoxy]phenyl]-2-ethoxypropanoate Chemical compound C=1C=C(OS(C)(=O)=O)C=CC=1CCOC1=CC(CC(OCC)C(=O)OCC)=CC=C1CC1=CC=CC=C1 VLJZDMUHOYNAJU-UHFFFAOYSA-N 0.000 claims description 2
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 2
235000019260 propionic acid Nutrition 0.000 claims 2
YRJFDAZUSIHIQN-UHFFFAOYSA-N 3-[3-benzyl-4-[2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]ethoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C=1C=CC=CC=1CC1=CC(CC(OCC)C(O)=O)=CC=C1OCCC1=CC=C(NC(=O)OC(C)(C)C)C=C1 YRJFDAZUSIHIQN-UHFFFAOYSA-N 0.000 claims 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 claims 1
SBKOOFCHZBMKBM-UHFFFAOYSA-N propan-2-yl 3-[4-benzyl-3-[2-(4-methylsulfonyloxyphenyl)ethoxy]phenyl]-2-ethoxypropanoate Chemical compound C=1C=C(OS(C)(=O)=O)C=CC=1CCOC1=CC(CC(OCC)C(=O)OC(C)C)=CC=C1CC1=CC=CC=C1 SBKOOFCHZBMKBM-UHFFFAOYSA-N 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
238000006243 chemical reaction Methods 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
125000000217 alkyl group Chemical group 0.000 description 46
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
239000000047 product Substances 0.000 description 40
238000005160 1H NMR spectroscopy Methods 0.000 description 35
229910052739 hydrogen Inorganic materials 0.000 description 33
239000001257 hydrogen Substances 0.000 description 33
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
239000000203 mixture Substances 0.000 description 31
125000002877 alkyl aryl group Chemical group 0.000 description 26
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
235000019439 ethyl acetate Nutrition 0.000 description 25
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 23
125000003118 aryl group Chemical group 0.000 description 23
239000012043 crude product Substances 0.000 description 21
125000006239 protecting group Chemical group 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
238000000034 method Methods 0.000 description 20
239000002904 solvent Substances 0.000 description 20
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
208000001072 type 2 diabetes mellitus Diseases 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
150000002431 hydrogen Chemical group 0.000 description 17
239000000243 solution Substances 0.000 description 17
239000007858 starting material Substances 0.000 description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
229940093499 ethyl acetate Drugs 0.000 description 16
229910052736 halogen Inorganic materials 0.000 description 16
150000002367 halogens Chemical class 0.000 description 16
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
125000004093 cyano group Chemical group *C#N 0.000 description 14
239000012074 organic phase Substances 0.000 description 14
239000012071 phase Substances 0.000 description 14
206010022489 Insulin Resistance Diseases 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
229910000027 potassium carbonate Inorganic materials 0.000 description 13
238000010561 standard procedure Methods 0.000 description 13
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
238000004587 chromatography analysis Methods 0.000 description 11
150000002148 esters Chemical class 0.000 description 11
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 11
239000012442 inert solvent Substances 0.000 description 10
238000002953 preparative HPLC Methods 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000010410 layer Substances 0.000 description 9
239000003921 oil Substances 0.000 description 9
238000000746 purification Methods 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000002585 base Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
238000003756 stirring Methods 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 6
239000005695 Ammonium acetate Substances 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 6
208000032928 Dyslipidaemia Diseases 0.000 description 6
238000006751 Mitsunobu reaction Methods 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
229940043376 ammonium acetate Drugs 0.000 description 6
235000019257 ammonium acetate Nutrition 0.000 description 6
239000000872 buffer Substances 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
239000003208 petroleum Substances 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
CBLURUVVHKBIPR-UHFFFAOYSA-N 2-(4-methylsulfonyloxyphenyl)ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1=CC=C(OS(C)(=O)=O)C=C1 CBLURUVVHKBIPR-UHFFFAOYSA-N 0.000 description 5
201000001320 Atherosclerosis Diseases 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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108010010234 HDL Lipoproteins Proteins 0.000 description 4
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108010007622 LDL Lipoproteins Proteins 0.000 description 4
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238000005481 NMR spectroscopy Methods 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
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108010062497 VLDL Lipoproteins Proteins 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
239000013058 crude material Substances 0.000 description 4
206010012601 diabetes mellitus Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
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239000012044 organic layer Substances 0.000 description 4
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LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 3
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239000012317 TBTU Substances 0.000 description 2
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KANUSUDVZCGLML-UHFFFAOYSA-N ethyl 3-(3-amino-4-hydroxyphenyl)-2-ethoxypropanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(O)C(N)=C1 KANUSUDVZCGLML-UHFFFAOYSA-N 0.000 description 1
KGDVVYBMDJBNAT-UHFFFAOYSA-N ethyl 3-(3-benzyl-4-hydroxyphenyl)-2-ethoxypropanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(O)C(CC=2C=CC=CC=2)=C1 KGDVVYBMDJBNAT-UHFFFAOYSA-N 0.000 description 1
CAKGNDFAOJOGQW-UHFFFAOYSA-N ethyl 3-(3-tert-butyl-4-hydroxyphenyl)-2-ethoxypropanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(O)C(C(C)(C)C)=C1 CAKGNDFAOJOGQW-UHFFFAOYSA-N 0.000 description 1
CSZVYDRIIALIBP-UHFFFAOYSA-N ethyl 3-(4-benzyl-3-hydroxyphenyl)-2-ethoxypropanoate Chemical compound OC1=CC(CC(OCC)C(=O)OCC)=CC=C1CC1=CC=CC=C1 CSZVYDRIIALIBP-UHFFFAOYSA-N 0.000 description 1
CRLZXWDQKKYSSP-UHFFFAOYSA-N ethyl 3-[3-benzyl-4-[2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]ethoxy]phenyl]-2-ethoxypropanoate Chemical compound C=1C=CC=CC=1CC1=CC(CC(OCC)C(=O)OCC)=CC=C1OCCC1=CC=C(NC(=O)OC(C)(C)C)C=C1 CRLZXWDQKKYSSP-UHFFFAOYSA-N 0.000 description 1
DYZWJGGNBISGJS-UHFFFAOYSA-N ethyl 3-[3-tert-butyl-4-[2-(4-methylsulfonyloxyphenyl)ethoxy]phenyl]-2-ethoxypropanoate Chemical compound CC(C)(C)C1=CC(CC(OCC)C(=O)OCC)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 DYZWJGGNBISGJS-UHFFFAOYSA-N 0.000 description 1
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239000000706 filtrate Substances 0.000 description 1
235000021588 free fatty acids Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
230000004153 glucose metabolism Effects 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
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FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000001511 high performance liquid chromatography nuclear magnetic resonance spectroscopy Methods 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
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239000012535 impurity Substances 0.000 description 1
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PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
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239000012280 lithium aluminium hydride Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
210000005228 liver tissue Anatomy 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000000155 melt Substances 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
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HXHDLPYZDLSIMR-UHFFFAOYSA-N methyl 3-benzyl-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C(CC=2C=CC=CC=2)=C1 HXHDLPYZDLSIMR-UHFFFAOYSA-N 0.000 description 1
BFSVAIKETYNYMW-UHFFFAOYSA-N methyl 4-benzyl-3-hydroxybenzoate Chemical compound OC1=CC(C(=O)OC)=CC=C1CC1=CC=CC=C1 BFSVAIKETYNYMW-UHFFFAOYSA-N 0.000 description 1
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125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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102000006255 nuclear receptors Human genes 0.000 description 1
108020004017 nuclear receptors Proteins 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
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150000002902 organometallic compounds Chemical class 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
238000005897 peptide coupling reaction Methods 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
238000001050 pharmacotherapy Methods 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
125000005633 phthalidyl group Chemical group 0.000 description 1
RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
201000010065 polycystic ovary syndrome Diseases 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
238000012552 review Methods 0.000 description 1
229910052702 rhenium Inorganic materials 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000000580 secretagogue effect Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229910001023 sodium amalgam Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
HJHVQCXHVMGZNC-JCJNLNMISA-M sodium;(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoate Chemical compound [Na+].O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C([O-])=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C HJHVQCXHVMGZNC-JCJNLNMISA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000006276 transfer reaction Methods 0.000 description 1
230000032258 transport Effects 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
229960001641 troglitazone Drugs 0.000 description 1
GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
231100000402 unacceptable toxicity Toxicity 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
230000009278 visceral effect Effects 0.000 description 1
239000011995 wilkinson's catalyst Substances 0.000 description 1
UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Emergency Medicine (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

AU20351/01A 1999-12-03 2000-11-29 New tri-substituted phenyl derivatives and analogues Ceased AU766533B2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
SE9904421		1999-12-03
SE9904421A SE9904421D0 (sv)	1999-12-03	1999-12-03	New compounds
PCT/SE2000/002385 WO2001040172A1 (en)	1999-12-03	2000-11-29	New tri-substituted phenyl derivatives and analogues

Publications (2)

Publication Number	Publication Date
AU2035101A AU2035101A (en)	2001-06-12
AU766533B2 true AU766533B2 (en)	2003-10-16

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AU20351/01A Ceased AU766533B2 (en)	1999-12-03	2000-11-29	New tri-substituted phenyl derivatives and analogues

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US (1)	US6750252B2 (zh)
EP (1)	EP1237856B1 (zh)
JP (1)	JP2003515583A (zh)
KR (1)	KR100787072B1 (zh)
CN (1)	CN1206212C (zh)
AR (1)	AR033957A1 (zh)
AT (1)	ATE266633T1 (zh)
AU (1)	AU766533B2 (zh)
BR (1)	BR0016130A (zh)
CA (1)	CA2392039A1 (zh)
DE (1)	DE60010747T2 (zh)
DK (1)	DK1237856T3 (zh)
ES (1)	ES2219425T3 (zh)
IL (2)	IL149517A0 (zh)
MX (1)	MXPA02005223A (zh)
MY (1)	MY124727A (zh)
NO (1)	NO20022590L (zh)
PT (1)	PT1237856E (zh)
SE (1)	SE9904421D0 (zh)
TR (1)	TR200401716T4 (zh)
TW (1)	TWI224590B (zh)
WO (1)	WO2001040172A1 (zh)
ZA (1)	ZA200203798B (zh)

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Publication number	Priority date	Publication date	Assignee	Title
US6369067B1 (en)	1997-10-27	2002-04-09	Dr. Reddy's Research Foundation	Monocyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them
WO1999016758A1 (en)	1997-10-27	1999-04-08	Dr. Reddy's Research Foundation	Novel heterocyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them
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SE0101386D0 (sv)	2001-04-20	2001-04-20	Astrazeneca Ab	New compounds
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1999
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2000
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Also Published As

Publication number	Publication date
AR033957A1 (es)	2004-01-21
KR100787072B1 (ko)	2007-12-21
EP1237856B1 (en)	2004-05-12
CN1402703A (zh)	2003-03-12
TWI224590B (en)	2004-12-01
AU2035101A (en)	2001-06-12
NO20022590D0 (no)	2002-05-31
JP2003515583A (ja)	2003-05-07
DE60010747D1 (de)	2004-06-17
TR200401716T4 (tr)	2004-09-21
MY124727A (en)	2006-06-30
US6750252B2 (en)	2004-06-15
KR20020067537A (ko)	2002-08-22
US20030149104A1 (en)	2003-08-07
DE60010747T2 (de)	2005-05-19
PT1237856E (pt)	2004-08-31
SE9904421D0 (sv)	1999-12-03
ES2219425T3 (es)	2004-12-01
EP1237856A1 (en)	2002-09-11
CN1206212C (zh)	2005-06-15
DK1237856T3 (da)	2004-08-02
ZA200203798B (en)	2003-10-29
IL149517A (en)	2007-07-04
NO20022590L (no)	2002-07-29
BR0016130A (pt)	2002-08-20
CA2392039A1 (en)	2001-06-07
ATE266633T1 (de)	2004-05-15
IL149517A0 (en)	2002-11-10
MXPA02005223A (es)	2003-09-25
WO2001040172A1 (en)	2001-06-07

Publication	Publication Date	Title
AU766533B2 (en)	2003-10-16	New tri-substituted phenyl derivatives and analogues
ES2209457T3 (es)	2004-06-16	Nuevos derivados del acido 3-aril-propionico, y analogos.
KR100625152B1 (ko)	2006-09-20	신규한 3-아릴-2-히드록시프로피온산 유도체 (ｉ)
EP1084101B1 (en)	2004-03-10	New 3-aryl-2-hydroxypropionic acid derivative iii
EP1237857B1 (en)	2004-06-30	New phenalkyloxy-phenyl derivatives
MXPA00011610A (en)	2001-09-07	New 3-aryl propionic acid derivatives and analogs

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